SPARC mediates tumour–stroma intercellular communication through endosomal regulation of Delta and Notch signalling
Abstract
Summary Tumour progression relies on reciprocal communication between genetically altered cancer cells and surrounding stromal cells. While the genetic alterations that initiate tumorigenesis have been extensively studied, the dysregulated feedback signalling provided by co-opted stromal cells remains poorly understood. Here, we used a Drosophila cancer model to address this question and identified the matricellular protein SPARC as a mediator of tumour–stroma communication. SPARC is produced by mesenchymal cells and transferred into epithelial tumour cells, where it is internalized through the endocytic pathway. Following uptake, SPARC accumulates in Rab7 positive late endosomes and colocalize with the Notch ligand Delta. SPARC internalization promotes endosomal enlargement and reduces endosome dynamics. Increased SPARC levels in epithelial tumours indirectly attenuate Notch signalling activity through at least altered Delta trafficking. We further identify the N-terminal acidic domain of SPARC as specifically required for its targeting to Delta-associated endosomes. Together, our findings uncover a stromal feedback mechanism by which SPARC modulates Notch signalling through endosomal regulation during tumour development.
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BibTeX
@misc{guillou2026sparc,
title = {{SPARC mediates tumour–stroma intercellular communication through endosomal regulation of Delta and Notch signalling}},
author = {Aurélien Guillou and Nourhene Ammar and Olivier Josse and Emma Leroux and Tsveta Kamenova and Torcato Martins and Samuel Delage and Maurice Joseph Ringuette and Sarah Bray and Hadi Boukhatmi},
howpublished = {BioRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.04.736483},
url = {https://hal.science/hal-05748892v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - SPARC mediates tumour–stroma intercellular communication through endosomal regulation of Delta and Notch signalling
AU - Aurélien Guillou
AU - Nourhene Ammar
AU - Olivier Josse
AU - Emma Leroux
AU - Tsveta Kamenova
AU - Torcato Martins
AU - Samuel Delage
AU - Maurice Joseph Ringuette
AU - Sarah Bray
AU - Hadi Boukhatmi
PY - 2026
DA - 2026/07/06
PB - BioRxiv
DO - 10.64898/2026.07.04.736483
UR - https://hal.science/hal-05748892v1
AB - Summary Tumour progression relies on reciprocal communication between genetically altered cancer cells and surrounding stromal cells. While the genetic alterations that initiate tumorigenesis have been extensively studied, the dysregulated feedback signalling provided by co-opted stromal cells remains poorly understood. Here, we used a Drosophila cancer model to address this question and identified the matricellular protein SPARC as a mediator of tumour–stroma communication. SPARC is produced by mesenchymal cells and transferred into epithelial tumour cells, where it is internalized through the endocytic pathway. Following uptake, SPARC accumulates in Rab7 positive late endosomes and colocalize with the Notch ligand Delta. SPARC internalization promotes endosomal enlargement and reduces endosome dynamics. Increased SPARC levels in epithelial tumours indirectly attenuate Notch signalling activity through at least altered Delta trafficking. We further identify the N-terminal acidic domain of SPARC as specifically required for its targeting to Delta-associated endosomes. Together, our findings uncover a stromal feedback mechanism by which SPARC modulates Notch signalling through endosomal regulation during tumour development.
SN - 2692-8205
ER -